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Casopitant: a novel NK(1)-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting.

Ruhlmann C, Herrstedt J - Ther Clin Risk Manag (2009)

Bottom Line: Chemotherapy-induced nausea and vomiting (CINV) are among the most feared and distressing symptoms experienced by patients with cancer.The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT)(3)- and neurokinin (NK)(1) receptors in the emetic reflex arch.This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors.

View Article: PubMed Central - PubMed

Affiliation: Odense University Hospital, Department of Oncology, Odense, Denmark.

ABSTRACT
Chemotherapy-induced nausea and vomiting (CINV) are among the most feared and distressing symptoms experienced by patients with cancer. The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT)(3)- and neurokinin (NK)(1) receptors in the emetic reflex arch. This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors. These drugs have had a huge impact in the protection from chemotherapy-induced vomiting, whereas the effect on nausea seems to be limited. The first NK(1) receptor antagonist, aprepitant, became clinically available in 2003, and casopitant, the second in this class of antiemetics, has now completed phase III trials. This review delineates the properties and clinical use of casopitant in the prevention of CINV.

No MeSH data available.


Related in: MedlinePlus

Patients (%) with complete response (120 h) in the phase III, HEC trial.46,47
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f2-tcrm-5-375: Patients (%) with complete response (120 h) in the phase III, HEC trial.46,47

Mentions: The phase III, HEC trial was conducted to assess the impact of casopitant, when used in combination with ondansetron and dexamethasone as compared to ondansetron and dexamethasone alone.46,47 810 patients received cisplatin-based chemotherapy in a dose of ≥70 mg/m2 and participated in a maximum of six cycles. The study was designed as multinational, double-blind and placebo-controlled. The control regimen consisted of ondansetron 32 mg IV plus dexamethasone 20 mg PO day 1, and dexamethasone 8 mg PO twice daily day 2–4 (Table 2). Patients were randomized to the control regimen or one of two experimental arms: a single dose of casopitant 150 mg PO; a three-day IV/oral dose, consisting of casopitant 90 mg IV day 1 and casopitant 50 mg PO day 2–3. The primary endpoint was complete response in the first 120 hours (CR, 120 h) after initiation of HEC. In the casopitant 150 mg PO day 1 arm a statistically significant increase of 20% (86% vs 66% in controls, p = 0.0001) in the number of patients with CR (120 h) was obtained (Figure 2), and this was maintained over multiple cycles. For the HEC regimen casopitant also demonstrated efficacy with regard to several secondary endpoints: CR (24 h) rates were 95% and 88% for the casopitant 150 mg and control groups, respectively (p = 0.0044); and interestingly improvements in no significant nausea (no SN), no nausea (NN) and no vomiting (NV) for both the acute and delayed phases, were observed as well.46 Casopitant given as a three-day IV/oral dose regimen also demonstrated to be superior to the control arm. CR (120 h) was achieved in 80% of patients (p = 0.0004) and CR (24 h) was 94% in this group (p = 0.0165), moreover efficacy was maintained over multiple cycles. Again clinically meaningful improvements were observed for no SN, NN, or NV.47 Casopitant was generally well tolerated. The most frequently reported side effects were neutropenia, leukopenia and anemia occurring with similar frequency in the experimental- and control arms.46,47


Casopitant: a novel NK(1)-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting.

Ruhlmann C, Herrstedt J - Ther Clin Risk Manag (2009)

Patients (%) with complete response (120 h) in the phase III, HEC trial.46,47
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2697542&req=5

f2-tcrm-5-375: Patients (%) with complete response (120 h) in the phase III, HEC trial.46,47
Mentions: The phase III, HEC trial was conducted to assess the impact of casopitant, when used in combination with ondansetron and dexamethasone as compared to ondansetron and dexamethasone alone.46,47 810 patients received cisplatin-based chemotherapy in a dose of ≥70 mg/m2 and participated in a maximum of six cycles. The study was designed as multinational, double-blind and placebo-controlled. The control regimen consisted of ondansetron 32 mg IV plus dexamethasone 20 mg PO day 1, and dexamethasone 8 mg PO twice daily day 2–4 (Table 2). Patients were randomized to the control regimen or one of two experimental arms: a single dose of casopitant 150 mg PO; a three-day IV/oral dose, consisting of casopitant 90 mg IV day 1 and casopitant 50 mg PO day 2–3. The primary endpoint was complete response in the first 120 hours (CR, 120 h) after initiation of HEC. In the casopitant 150 mg PO day 1 arm a statistically significant increase of 20% (86% vs 66% in controls, p = 0.0001) in the number of patients with CR (120 h) was obtained (Figure 2), and this was maintained over multiple cycles. For the HEC regimen casopitant also demonstrated efficacy with regard to several secondary endpoints: CR (24 h) rates were 95% and 88% for the casopitant 150 mg and control groups, respectively (p = 0.0044); and interestingly improvements in no significant nausea (no SN), no nausea (NN) and no vomiting (NV) for both the acute and delayed phases, were observed as well.46 Casopitant given as a three-day IV/oral dose regimen also demonstrated to be superior to the control arm. CR (120 h) was achieved in 80% of patients (p = 0.0004) and CR (24 h) was 94% in this group (p = 0.0165), moreover efficacy was maintained over multiple cycles. Again clinically meaningful improvements were observed for no SN, NN, or NV.47 Casopitant was generally well tolerated. The most frequently reported side effects were neutropenia, leukopenia and anemia occurring with similar frequency in the experimental- and control arms.46,47

Bottom Line: Chemotherapy-induced nausea and vomiting (CINV) are among the most feared and distressing symptoms experienced by patients with cancer.The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT)(3)- and neurokinin (NK)(1) receptors in the emetic reflex arch.This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors.

View Article: PubMed Central - PubMed

Affiliation: Odense University Hospital, Department of Oncology, Odense, Denmark.

ABSTRACT
Chemotherapy-induced nausea and vomiting (CINV) are among the most feared and distressing symptoms experienced by patients with cancer. The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT)(3)- and neurokinin (NK)(1) receptors in the emetic reflex arch. This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors. These drugs have had a huge impact in the protection from chemotherapy-induced vomiting, whereas the effect on nausea seems to be limited. The first NK(1) receptor antagonist, aprepitant, became clinically available in 2003, and casopitant, the second in this class of antiemetics, has now completed phase III trials. This review delineates the properties and clinical use of casopitant in the prevention of CINV.

No MeSH data available.


Related in: MedlinePlus